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| 7. |
- Isobe, T, et al.
(författare)
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Multi-omics analysis defines highly refractory RAS burdened immature subgroup of infant acute lymphoblastic leukemia
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4501-
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Tidskriftsartikel (refereegranskat)abstract
- KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) represents the most refractory type of childhood leukemia. To uncover the molecular heterogeneity of this disease, we perform RNA sequencing, methylation array analysis, whole exome and targeted deep sequencing on 84 infants with KMT2A-rearranged leukemia. Our multi-omics clustering followed by single-sample and single-cell inference of hematopoietic differentiation establishes five robust integrative clusters (ICs) with different master transcription factors, fusion partners and corresponding stages of B-lymphopoietic and early hemato-endothelial development: IRX-type differentiated (IC1), IRX-type undifferentiated (IC2), HOXA-type MLLT1 (IC3), HOXA-type MLLT3 (IC4), and HOXA-type AFF1 (IC5). Importantly, our deep mutational analysis reveals that the number of RAS pathway mutations predicts prognosis and that the most refractory subgroup of IC2 possesses 100% frequency and the heaviest burden of RAS pathway mutations. Our findings highlight the previously under-appreciated intra- and inter-patient heterogeneity of KMT2A-rearranged infant ALL and provide a rationale for the future development of genomics-guided risk stratification and individualized therapy.
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- Aharonian, Felix, et al.
(författare)
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Hitomi X-ray studies of giant radio pulses from the Crab pulsar
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)abstract
- To search for giant X-ray pulses correlated with the giant radio pulses (GRPs) from the Crab pulsar, we performed a simultaneous observation of the Crab pulsar with the X-ray satellite Hitomi in the 2-300 keV band and the Kashima NICT radio telescope in the 1.4-1.7 GHz band with a net exposure of about 2 ks on 2016 March 25, just before the loss of the Hitomi mission. The timing performance of the Hitomi instruments was confirmed to meet the timing requirement and about 1000 and 100 GRPs were simultaneously observed at the main pulse and inter-pulse phases, respectively, and we found no apparent correlation between the giant radio pulses and the X-ray emission in either the main pulse or inter-pulse phase. All variations are within the 2 sigma fluctuations of the X-ray fluxes at the pulse peaks, and the 3 sigma upper limits of variations of main pulse or inter-pulse GRPs are 22% or 80% of the peak flux in a 0.20 phase width, respectively, in the 2-300 keV band. The values for main pulse or inter-pulse GRPs become 25% or 110%, respectively, when the phase width is restricted to the 0.03 phase. Among the upper limits from the Hitomi satellite, those in the 4.5-10 keV and 70-300 keV bands are obtained for the first time, and those in other bands are consistent with previous reports. Numerically, the upper limits of the main pulse and inter-pulse GRPs in the 0.20 phase width are about (2.4 and 9.3) x 10(-11) erg cm(-2), respectively. No significant variability in pulse profiles implies that the GRPs originated from a local place within the magneto-sphere. Although the number of photon-emitting particles should temporarily increase to account for the brightening of the radio emission, the results do not statistically rule out variations correlated with the GRPs, because the possible X-ray enhancement may appear due to a > 0.02% brightening of the pulse-peak flux under such conditions.
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| 10. |
- Ochi, Y, et al.
(författare)
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Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2833-
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Tidskriftsartikel (refereegranskat)abstract
- Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML.
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- Lundberg, Jon O., et al.
(författare)
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Nitrate and nitrite in biology, nutrition and therapeutics
- 2009
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Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 5:12, s. 865-869
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Tidskriftsartikel (refereegranskat)abstract
- Inorganic nitrate and nitrite from endogenous or dietary sources are metabolized in vivo to nitric oxide (NO) and other bioactive nitrogen oxides. The nitrate-nitrite-NO pathway is emerging as an important mediator of blood flow regulation, cell signaling, energetics and tissue responses to hypoxia. The latest advances in our understanding of the biochemistry, physiology and therapeutics of nitrate, nitrite and NO were discussed during a recent 2-day meeting at the Nobel Forum, Karolinska Institutet in Stockholm.
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- Oyama, S., et al.
(författare)
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An Ephemeral Red Arc Appeared at 68 degrees MLat at a Pseudo Breakup During Geomagnetically Quiet Conditions
- 2020
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 125:10
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Tidskriftsartikel (refereegranskat)abstract
- Various subauroral optical features have been studied by analyzing data collected during periods of geomagnetic disturbances. Most events have been typically found at geomagnetic latitudes of 45-60 degrees. In this study, however, we present a red arc event found at geomagnetic 68 degrees north (L approximate to 7.1) in the Scandinavian sector during a period of geomagnetically quiet conditions within a short intermission between two high-speed solar wind events. The red arc appeared to coincide with a pseudo breakup at geomagnetic 71-72 degrees N and a rapid equatorward expansion of the polar cap. However, the red arc disappeared in approximately 7 min. Simultaneous measurements with the Swarm A/C satellites indicated the appearance of the red arc at the ionospheric trough minimum and a conspicuous enhancement of the electron temperature, suggesting the generation of the arc by heat flux. Since there are meaningful differences in the red arc features from already-known subauroral optical features such as the stable auroral red (SAR) arc, we considered that the red arc is a new phenomenon. We suggest that the ephemeral red arc may represent the moment of SAR arc birth associated with substorm particle injection, which is generally masked by bright dynamic aurorae.
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| 18. |
- Powles, T, et al.
(författare)
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Plain language summary of results from the JAVELIN Bladder 100 study: avelumab maintenance treatment for advanced urothelial cancer
- 2022
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Ingår i: Future oncology (London, England). - : Future Medicine Ltd. - 1744-8301 .- 1479-6694. ; 18:19, s. 2361-2371
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Tidskriftsartikel (refereegranskat)abstract
- This is a plain language summary of an article originally published in The New England Journal of Medicine. It is about initial results (collected in October 2019) from the JAVELIN Bladder 100 study (a clinical trial), which looked at avelumab maintenance treatment in people with advanced urothelial cancer. Urothelial cancer is the most common type of bladder cancer. People with advanced urothelial cancer often receive chemotherapy. If this is the first treatment people with advanced disease are given, it is called first-line treatment. If the cancer stops growing or shrinks with first-line chemotherapy, people can be given different treatment to try to prevent the cancer from growing again. This is called maintenance treatment. It may help people live longer. What happened in the JAVELIN Bladder 100 study? In the JAVELIN Bladder 100 study, researchers wanted to find out if maintenance treatment with avelumab would help people with advanced urothelial cancer live longer. Avelumab is a type of medicine called immunotherapy. Immunotherapy helps the body's immune system fight cancer. 700 people took part in the study. To take part, they must have already been treated with first-line chemotherapy. Also, their cancer must have shrunk or not grown with this treatment. They were then treated with either avelumab maintenance treatment plus best supportive care or best supportive care alone. Best supportive care means treatments that help improve symptoms and quality of life. These treatments do not affect the cancer directly and can include medicines to relieve pain. What were the results? Researchers found that people treated with avelumab maintenance treatment plus best supportive care lived, on average, 7 months longer than people who received best supportive care alone. People treated with avelumab had more side effects than those not treated with avelumab, but most were not severe. Common side effects with avelumab included persistent tiredness, itchy skin, urinary tract infection, and diarrhea. What do the results of the study mean? Results from the JAVELIN Bladder 100 study support the use of avelumab as maintenance treatment for people with advanced urothelial cancer whose cancer has shrunk or not grown with first-line chemotherapy. ClinicalTrials.gov NCT number: NCT02603432
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| 19. |
- Shoji, Y., et al.
(författare)
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An Element-Substituted Cyclobutadiene Exhibiting High-Energy Blue Phosphorescence
- 2021
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Ingår i: Angewandte Chemie International Edition. - : John Wiley and Sons Inc. - 1433-7851 .- 1521-3773. ; 60:40, s. 21817-21823
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Tidskriftsartikel (refereegranskat)abstract
- 1,3,2,4-Diazadiboretidine, an isoelectronic heteroanalogue of cyclobutadiene, is an interesting chemical species in terms of comparison with the carbon system, whereas its properties have never been investigated experimentally. According to Baird's rule, Hückel antiaromatic cyclobutadiene acquires aromaticity in the lowest triplet state. Here we report experimental and theoretical studies on the ground- and excited-state antiaromaticity/aromaticity as well as the photophysical properties of an isolable 1,3,2,4-diazadiboretidine derivative. The crystal structure of the diazadiboretidine derivative revealed that the B2N2 ring adopts a planar rhombic geometry in the ground state. Yet, theoretical calculations showed that the B2N2 ring turns to a square geometry with a nonaromatic character in the lowest triplet state. Notably, the diazadiboretidine derivative has the lowest singlet and triplet states lying at close energy levels and displays blue phosphorescence.
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| 20. |
- Shoji, Yoshiaki, et al.
(författare)
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Inside Cover : An Element-Substituted Cyclobutadiene Exhibiting High-Energy Blue Phosphorescence (Angew. Chem. Int. Ed. 40/2021)
- 2021
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Ingår i: Angewandte Chemie International Edition. - : John Wiley & Sons. - 1433-7851 .- 1521-3773. ; 60:40, s. 21598-21598
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Tidskriftsartikel (refereegranskat)abstract
- The ground- and excited-state properties of a diazadiboretidine (DADBT) derivative, an isoelectronic heterocyclic analogue of cyclobutadiene, are reported by Henrik Ottosson, Hiromi Nakai, Tadaaki Ikoma, Takanori Fukushima, and co-workers in their Research Article on page 21817. While the B2N2 ring of the DADBT derivative adopts a rhombic geometry in the ground state, it turns to a square geometry with a nonaromatic character in the lowest triplet state. Notably, the DADBT derivative displays blue phosphorescence in solution, providing insight into the photophysical properties of heterocyclic pi-systems.+
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| 22. |
- Taniyasu, Sachi, et al.
(författare)
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Inter-laboratory trials for analysis of perfluorooctanesulfonate and perfluorooctanoate in water samples : Performance and recommendations
- 2013
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Ingår i: Analytica Chimica Acta. - : Elsevier. - 0003-2670 .- 1873-4324. ; 770, s. 111-120
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Tidskriftsartikel (refereegranskat)abstract
- The ISO 25101 (International Organization for Standardization, Geneva) describes a new international standard method for the determination of perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) in unfiltered samples of drinking and surface waters. The method is based on the extraction of target analytes by solid phase extraction, solvent elution, and determination by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). For the determination of the performance of this method, more than 20 laboratories from 9 different countries participated in an inter-laboratory trial in 2006. In addition, inter-laboratory trials were conducted in 2008 and 2009 for the analysis of perfluoroalkylsubstances (PFASs), including PFOS and PFOA, in water samples by following the protocols of Japanese Industrial Standard (JIS). Overall, the repeatability coefficients of variation (i.e., within-laboratory precision) for PFOS and PFOA in all water samples were between 3 and 11%, showing a adequate precision of the ISO and JIS methods. The reproducibility coefficients of variation (i.e., between-laboratory precision) were found to vary within a range of 7-31% for surface water and 20-40% for wastewater. The recoveries of PFOS and PFOA, as a measure of accuracy, varied from 84 to 100% for surface water and from 84 to 100% for wastewater among the samples with acceptable criteria for internal standards recovery. The determined concentrations of PFASs in samples compared well with the " true" values. The results of the inter-laboratory trial confirmed that the analytical methods are robust and reliable and can be used as a standard method for the analysis of target compounds in water samples.
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| 23. |
- Tiemeyer, Michael, et al.
(författare)
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GlyTouCan: an accessible glycan structure repository.
- 2017
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 27:10, s. 915-919
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Tidskriftsartikel (refereegranskat)abstract
- Rapid and continued growth in the generation of glycomic data has revealed the need for enhanced development of basic infrastructure for presenting and interpreting these datasets in a manner that engages the broader biomedical research community. Early in their growth, the genomic and proteomic fields implemented mechanisms for assigning unique gene and protein identifiers that were essential for organizing data presentation and for enhancing bioinformatic approaches to extracting knowledge. Similar unique identifiers are currently absent from glycomic data. In order to facilitate continued growth and expanded accessibility of glycomic data, the authors strongly encourage the glycomics community to coordinate the submission of their glycan structures to the GlyTouCan Repository and to make use of GlyTouCan identifiers in their communications and publications. The authors also deeply encourage journals to recommend a submission workflow in which submitted publications utilize GlyTouCan identifiers as a standard reference for explicitly describing glycan structures cited in manuscripts.
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